The overarching theme of the proposed Penn Mental Health AIDS Research Center (PMHARC) at the University of Pennsylvania (Penn) and Children's Hospital of Philadelphia (CHOP) is to transform how individuals with comorbid mental illness/AIDS are treated and managed by developing innovative, interdisciplinary, and integrative approaches to optimize psychiatric, behavioral, and medical outcomes and achieving a better understanding of the biological, psychological, and behavioral mechanisms underlying these combined illnesses and treatments. No other center in the U.S. is currently pursuing this explicit focus, making PMHARC unique in the NIMH ARC portfolio. A substantial body of work links psychiatric disorders to acquisition of HIV infection, accelerated immune dysfunction, poor access to HIV care, and poor adherence to antiretroviral treatment once in care. Yet, there is a relative paucity of evidence-based interventions focused on the combined treatment of mental illness/AIDS and related medical co-morbidities, and relatively little work in determining the relationships between mental health treatment and HIV/AIDS disease and understanding the underlying biology. PMHARC will stimulate novel approaches and strategies to address these problems by providing mentoring and resource support for both new and established investigators choosing to study comorbid mental illness/AIDS, in part through innovative pilot studies. PMHARC's leadership has extensive expertise in contemporary pharmacotherapy of mental illness and AIDS, cognitive behavioral treatments, and theory-based behavioral interventions. PMHARC will extend well-established collaborations at Penn and CHOP, including those in the Department of Psychiatry and Penn Center for AIDS Research (CFAR), as well as with community partners in Philadelphia. A unique feature of PMHARC is the collaboration of well-established mental health AIDS researchers, well-established mental health researchers who have not previously studied AIDS, well-established substance abuse AIDS researchers who have not previously studied mental health, and AIDS researchers not previously focused on mental health. PMHARC will have an Administrative and Developmental Core, and four Shared Resource Cores.